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Association between Insertion/Deletion Polymorphism in Angiotension Converting Enzyme and Susceptibility to Schizophrenia.

ABSTRACT: BACKGROUND:The activity of angiotension converting enzyme (ACE; OMIM: 106180) in different brain regions of patients with schizophrenia changed, suggesting a possible involvement of ACE in psychiatric disorders. Genetic polymorphism of insertion/deletion (I/D; dbSNP rs4646994) in the gene encoding ACE has been well defined. METHODS:The present case-control study was performed on 363 (268 males, 95 females) in-patients with schizophrenia diagnosis, and 363 (268 males, 95 females) healthy blood donor controls. The genotypes of I/D ACE polymorphism were determined using PCR method. PCR products were separated and sized by electrophoresis on a 2% agarose gel. The insertion allele (I) was detected as a 478 bp band, and the deletion allele (D) was visualized as a 191 bp band. The association between genotypes of the I/D polymorphism and the schizophrenia risk was examined by use of odds ratios (OR) and 95% of confidence intervals (CIs). RESULTS:Among females, the II genotype significantly decreased the risk of schizophrenia compared with the DD genotype (OR=0.18, 95%CI: 0.04-0.72, P=0.015). There was significant linear trend for the number of the I allele and schizophrenia risk among females (Chi(2)=5.19, P=0.023). There was no significant association between I/D polymorphism and susceptibility to schizophrenia among male subjects. There was significant interaction between gender and the II genotype (P=0.031). CONCLUSION:The II genotype of the I/D polymorphism has a protective effect for schizophrenia among females.

SUBMITTER: Mazaheri H

PROVIDER: S-EPMC4402415 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Association between Insertion/Deletion Polymorphism in Angiotension Converting Enzyme and Susceptibility to Schizophrenia.

Mazaheri Hajar H Saadat Mostafa M

Iranian journal of public health 20150301 3

<h4>Background</h4>The activity of angiotension converting enzyme (ACE; OMIM: 106180) in different brain regions of patients with schizophrenia changed, suggesting a possible involvement of ACE in psychiatric disorders. Genetic polymorphism of insertion/deletion (I/D; dbSNP rs4646994) in the gene encoding ACE has been well defined.<h4>Methods</h4>The present case-control study was performed on 363 (268 males, 95 females) in-patients with schizophrenia diagnosis, and 363 (268 males, 95 females) h ...[more]

PMID: 25905080

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Project description:ObjectiveBlood-borne angiotensin II is generated from angiotensinogen via cleavage by renin and angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system (RAS). Several lines of evidence indicate that ACE, beyond its classical role of mediating blood pressure regulation, might contribute to the etiology of substance addictions by influencing dopaminergic signaling. A functional insertion/deletion (I/D) polymorphism of the ACE gene was associated with risk for being a smoker among individuals with depression and with smoking severity in studies comprising patients with depression and healthy controls. Several reports have described significantly increased ACE activity in cerebrospinal fluid and serum among MS patients. Furthermore, in our previous work with MS patients from Croatian and Slovenian populations, we demonstrated that the ACE-I/D polymorphism contributes to an elevated MS risk among male patients. Here we investigated whether the ACE-I/D polymorphism might influence smoking behavior among patients with MS.Patients and methodsGenotyping was performed in 521 patients (males/females: 139/382) using polymerase chain reaction.ResultsWe revealed no significant differences in ACE genotype and allele frequencies between smokers and nonsmokers and no significant association between the ACE-I/D polymorphism and either pack-year smoking history or number of cigarettes smoked daily (p > .05, respectively).ConclusionThe ACE-I/D polymorphism does not contribute either to risk for nicotine dependence or to smoking severity among MS patients. In the context of reports on the ACE-I/D polymorphism and nicotine dependence among healthy controls and patients with depression, we may speculate that the mechanism by which this polymorphism influences nicotine dependence risk differs in MS compared to depression, although not compared to a healthy population. In addition to angiotensin II, other potential ACE substrates, such as substance P and neurotensin, which also influence dopaminergic neurotransmission (and are proposed to be associated with MS), may deserve study in future.

Project description:ObjectiveA silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle.MethodsFifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc.ResultsCycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and -3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon.ConclusionThe observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.

Project description:Background and purposeThe angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs.MethodsThe CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes.ResultsAmong 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02).ConclusionThe progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.

Dataset Information

Association between Insertion/Deletion Polymorphism in Angiotension Converting Enzyme and Susceptibility to Schizophrenia.

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Association between Insertion/Deletion Polymorphism in Angiotension Converting Enzyme and Susceptibility to Schizophrenia.

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